The Liston laboratory works on regulatory T cells. These are a type of white blood cell that act to suppress the rest of the immune response, preventing spontaneous autoimmune disease and acting as a rheostat to control just how active our immune system is. The number of these cells in our blood goes up as we get old, which may contribute to the immune-suppressed state of older persons. We seek to understand these cells, using both patient material and mouse models, so that we can harness their power to fine-tune the immune system for healthy ageing.
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T follicular helper (T) cells are a helper T-cell subset that is defined by their localisation to B-cell areas of secondary lymphoid tissues, enabling them to provide their B-cell helper function. Precursors of T cells migrate to the B-cell follicles by upregulating CXCR5 and downregulating CCR7, a process that can be blocked by S1PR1 overexpression. T cells and their precursors also express the early activation antigen CD69, which is a negative regulator of S1PR1. In this study, we tested the hypothesis that CD69 expression by T cells is important for their differentiation and localisation after immunization. Genetic deletion of CD69 on T cells and a proportion of their precursors did not alter their formation, nor their ability to support high-affinity B-cell responses. This demonstrates that although CD69 is expressed highly on T cells, it is not necessary for their formation or their B-cell helper functions in lymph nodes (LNs).
Solid-organ transplant (SOT) recipients are at enhanced risk of infection and to poorly respond to vaccination due to comorbidities and immunosuppression. We performed a systems vaccinology study in 59 kidney and 31 lung transplant recipients who received 3 doses of COVID-19 mRNA BNT162b2 vaccine. We were able to characterize a baseline configuration associated with an effective humoral response to 3 doses, characterized by an innate and activated B cell profile, whereas a T cell signature was associated with a poorer response. We observed a distinct configuration associated with a detectable humoral response to 2 doses, partly mediated by double negative B cell subsets. These results suggest that, despite their immunosuppression, some SOT recipients can induce an effective humoral response to 3 doses of vaccine supported by a baseline configuration close to the healthy phenotype. Baseline immune phenotyping may help identify SOT recipients at the greatest risk of a poor vaccine response.